Pregelatinized starch in a controlled release formulation

Abstract

The present invention concerns the use of pregelatinized starch to prevent dose-dumping from a hydrophilic controlled release formulation. It also concerns a hydrophilic controlled release formulation, more in particular a hydrophilic controlled release matrix formulation, and solid dosage forms prepared therefrom, preferably for once daily oral administration. The hydrophilic controlled release formulation comprises pregelatinized starch, one or more active ingredients, one or more viscous hydrophilic polymers and optionally pharmaceutically acceptable formulating agents. Preferred hydrophilic polymers include hydroxypropyl cellulose and hydroxypropyl methylcellulose.

The invention claimed is: 
     
       1. A hydrophilic controlled release solid tablet formulation comprising a matrix comprising, as a substantially homogeneous admixture:
 about 5% to less than 80%, by weight of the tablet, of pregelatinized starch 
 an active ingredient that is 9-hydroxyrisperidone, a pharmaceutically acceptable acid addition salt thereof, an N-oxide form thereof, or a stereochemically isomeric form thereof, and 
 one or more viscous hydrophilic polymers, 
 wherein said controlled release solid tablet formulation allows at least a two-fold reduction in dosing frequency, an increase in patient compliance, or an increase in therapeutic performance, as compared to a conventional 9-hydroxyrisperidone dosage form. 
 
     
     
       2. The controlled release solid tablet formulation of  claim 1 , wherein said one or more hydrophilic polymers are selected from the group consisting of alkylcellulose, hydroxyalkylcellulose, hydroxyalkylalkylcellulose, carboxyalkylcellulose, alkali metal salts of carboxyalkylcellulose, natural, semi synthetic or synthetic polysaccharide, polyacrylic acid and salts thereof, polymethacrylic acid and the salts thereof, polyvinyl alcohol, polyvinylpyrrolidone, and polyalkylene oxides. 
     
     
       3. The controlled release solid tablet formulation of  claim 1 , wherein said one or more hydrophilic polymers are selected from the group consisting of hydroxypropyl cellulose and hydroxypropylmethylcellulose. 
     
     
       4. The controlled release solid tablet formulation of  claim 3 , wherein said hydroxypropylmethylcellulose has a viscosity in a range from about 3,500 mPa·s to about 100,000 mPa·s. 
     
     
       5. The controlled release solid tablet formulation of  claim 3 , wherein said hydroxypropylcellulose has a viscosity of less than about 1,500 mPa·s. 
     
     
       6. The controlled release solid tablet formulation of  claim 1 , wherein said one or more hydrophilic polymers are present in an amount from about 0.01 to about 80% by weight of the tablet. 
     
     
       7. The controlled release solid tablet formulation of  claim 1 , wherein at least two hydrophilic polymers are present in said formulation. 
     
     
       8. The controlled release solid tablet formulation of  claim 7 , wherein said at least two hydrophilic polymers are hydroxypropylcellulose and hydroxypropylmethylcellulose. 
     
     
       9. The controlled release solid tablet formulation of  claim 8 , wherein a ratio of said hydroxypropylcellulose to said hydroxypropylmethylcellulose ranges from 1:5 to 5:1. 
     
     
       10. The controlled release solid tablet formulation of  claim 1 , wherein said pregelatinized starch is present at about 5% (w/w), by weight of the tablet. 
     
     
       11. The controlled release solid tablet formulation of  claim 1 , wherein said pregelatinized starch is present at about 5% to about 15%, by weight of the tablet. 
     
     
       12. A method of providing controlled release of 9-hydroxyrisperidone, a pharmaceutically acceptable acid addition salt thereof, an N-oxide form thereof, or a stereochemically isomeric form thereof, in a subject, comprising administering the controlled release solid tablet formulation of  claim 1  to said subject. 
     
     
       13. A method of preparing a controlled release solid tablet formulation comprising mixing 9-hydroxyrisperidone, a pharmaceutically acceptable acid addition salt thereof, an N-oxide form thereof, or a stereochemically isomeric form thereof with about 5% to less than 80%, by weight of the tablet, of pregelatinized starch and one or more hydrophilic polymers, to provide a substantially homogeneous admixture thereof, such that said controlled release solid tablet formulation allows at least a two-fold reduction in dosing frequency, an increase in patient compliance, or an increase in therapeutic performance, as compared to a conventional 9-hydroxyrisperidone dosage form. 
     
     
       14. The controlled release solid tablet formulation according to  claim 1  wherein the tablet consists essentially of an optional coating and a controlled release matrix comprising a substantially homogeneous admixture comprising said active ingredient, said one or more viscous hydrophilic polymers, and said pregelatinized starch.